Abstract

NSAIDs are prescribed widely but have rare serious gastrointestinal side effects.
More recently, adverse cardiovascular effects of these drugs have also been recognized,
leading to the withdrawal of some agents and continuing uncertainty about the best
approach for patients requiring NSAID therapy. Proton pump inhibitors (PPIs) provide
potent and long-lasting inhibition of gastric acid secretion and have proven efficacy
in healing NSAID-associated ulcers, including those with continued exposure to NSAIDs.
PPIs have also shown efficacy in reducing the risk of ulcerations due to NSAID use
compared with NSAIDs alone in randomized controlled trials (RCTs) where endoscopic
ulcers are used as the primary endpoint, albeit a surrogate marker for clinical ulcers
and complications. Large RCT outcome trials comparing patients exposed to NSAIDs with
and without PPI co-therapy have not been performed, but adequately powered RCTs in
high-risk patients demonstrate that PPI + nonselective NSAID provides similar rates
of symptomatic ulcer recurrence rates as the use of a cyclooxygenase (COX)-2 selective
inhibitor. A RCT in high-risk patients with previous ulcer complications supports
the additive bene3 t of two risk-reducing strategies, as ulcer complication recurrence
was eliminated in high-risk patients who were given a COX-2 selective agent with a
PPI. Helicobacter pylori, an independent risk factor for ulcers, should be sought out and eradicated in patients
at increased gastrointestinal risk, typically those with an ulcer history. Following
H. pylori eradication, however, patients remain at risk and co-therapy with a PPI is recommended.
NSAID medication selection should consider both the individual patients' gastrointestinal
and cardiovascular risks.